Fig. 4.

Aspartate (D) scan of the central cavity supports an electrostatic mechanism for K⁺ selectivity. (A) Side view of the Kir3.2 channel with the S177W (red) mutation on the M2 helix. In the cavity, three residues from two faces, face 1 (green) and face 2 (red), are shown. Residues that were subjected to Asp (D) substitution are as follows: on face 1, G180, N184, and V188; on face 2, S181, A185, and G189. (B) Asp (D) substitution of residues at every position on face 1 (green), but at none of the positions on face 2 (red), restores K⁺ selectivity, as shown by values of the Na⁺ and K⁺ permeability ratio deduced from the difference in reversal potential measured in 90 mM Na⁺ and 90 mM K⁺ solutions. Values are mean ± SEM; values for selective channels are TPN_Q-corrected. ∗, P < 0.001. (C) Molecular surface representation of the Kir3.2 cavity viewed from the extracellular side. Residues on face 1 (green) are closer to the cavity ion (blue) and have greater solvent exposure than the residues on face 2 (red).